In vitro and in vivo oxidative metabolism and glucuronidation of anastrozole.

ABSTRACT:

Aims

Little information is available regarding the metabolic routes of anastrozole and the specific enzymes involved. We characterized anastrozole oxidative and conjugation metabolism in vitro and in vivo.

Methods

A sensitive LC-MS/MS method was developed to measure anastrozole and its metabolites in vitro and in vivo. Anastrozole metabolism was characterized using human liver microsomes (HLMs), expressed cytochrome P450s (CYPs) and UDP-glucuronosyltransferases (UGTs).

Results

Hydroxyanastrozole and anastrozole glucuronide were identified as the main oxidative and conjugated metabolites of anastrozole in vitro, respectively. Formation of hydroxyanastrozole from anastrozole was markedly inhibited by CYP3A selective chemical inhibitors (by >90%) and significantly correl

SUBMITTER: Kamdem LK 

PROVIDER: S-EPMC3014069 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature